Rotavirus-Induced Expansion of Antigen-Specific CD8 T Cells Does Not Require Signaling via TLR3, MyD88 or the Type I Interferon Receptor

Muleta, Konjit Getachew; Ulmert, Isabel; Hamza, Kedir Hussen; Dijl, Sharné van; Nakawesi, Joy; Lahl, Katharina

doi:10.3389/fimmu.2022.814491

Cited by 4 publications

(2 citation statements)

References 55 publications

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“…infection [56]. Additionally, we show for the first time that RV is capable of infecting tumor vasculature, but the vascular endothelium in non-tumor tissues is resistant to virus infection.…”

Section: Plos Onementioning

confidence: 71%

“…Rotaviruses are initially recognized by pattern recognition receptors (PRRs) in cells of the innate immune system such as macrophages and classical type I dendritic cells (cDC1) [ 55 ]. cDC1 excel at inducing CD8 T cells through cross-presentation, which is essential for optimal RV cytotoxicity, promoting strong adaptive immunity against RV infection [ 56 ]. Additionally, we show for the first time that RV is capable of infecting tumor vasculature, but the vascular endothelium in non-tumor tissues is resistant to virus infection.…”

Section: Discussionmentioning

confidence: 99%

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Preclinical evaluation of oncolytic potential human rotavirus Wt 1-5 in gastric adenocarcinoma

et al. 2023

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Despite advances in biomedical research, gastric cancer remains the leading cause of morbidity and mortality worldwide due to the limited efficacy of conventional therapies. In recent decades, oncolytic viruses have emerged as a biological therapeutic alternative to cancer due to their selectivity, effectiveness, and low toxicity. However, clinical trials have shown that developing a virus with selectivity for multiple tumor receptors and the ability to penetrate and diffuse through the tumor microenvironment to reactivate the immune system remains challenging. This study aimed to examine the oncolytic potential of tumor cell-adapted rotavirus Wt1-5 in gastric adenocarcinoma samples. This study focused on determining the propagation capacity of the RV Wt1-5 through the tumor and the importance of the expression of cell surface co-receptors, including integrin β3, protein disulfide isomerase (PDI), and heat shock proteins (Hsp-90, -70, -60, -40, and Hsc 70), during infection of tumor cells. These proteins were found to be differentially expressed in tumor cells compared to adjacent non-tumor cells. Preincubation of gastric tumor cells with antibodies against these proteins decreased rotavirus infections, validating their importance in the binding and entry of RV Wt1-5 into tumor cells, as previously reported. Upon RV infection, apoptosis was one of the types of death that was observed. This was evidenced by evaluating the expression of CASP-3, -9, PARP, cytochrome C, Bax, Bid, p53, and Bcl-2, as well as observing morphological changes such as chromatin margination, nuclear condensation, and fragmentation. Finally, at 60 h.p.i, histological analysis revealed that oncolysis compromised the entire thickness of the tumor. Therefore, the results suggest that RV Wt1-5 could be a novel therapeutic agent co-adjuvant agent for conventional and targeted therapies in managing GC. Ex vivo infection of the tumor tissue model showed characteristics of an immune response that could be explored in future studies.

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Section: Plos Onementioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Preclinical evaluation of oncolytic potential human rotavirus Wt 1-5 in gastric adenocarcinoma

et al. 2023

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Identification and Characterization of Antigen-Specific T-Cells in Viral Infections

Trubach,

Muleta,

Lahl

et al. 2024

Methods in Molecular Biology

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Sequential early-life viral infections modulate the microbiota and adaptive immune responses to systemic and mucosal vaccination

Li,

Molleston,

Lovato

et al. 2024

PLoS Pathog

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Increasing evidence points to the microbial exposome as a critical factor in maturing and shaping the host immune system, thereby influencing responses to immune challenges such as infections or vaccines. To investigate the effect of early-life viral exposures on immune development and vaccine responses, we inoculated mice with six distinct viral pathogens in sequence beginning in the neonatal period, and then evaluated their immune signatures before and after intramuscular or intranasal vaccination against SARS-CoV-2. Sequential viral infection drove profound changes in all aspects of the immune system, including increasing circulating leukocytes, altering innate and adaptive immune cell lineages in tissues, and markedly influencing serum cytokine and total antibody levels. Beyond changes in the immune responses, these exposures also modulated the composition of the endogenous intestinal microbiota. Although sequentially-infected mice exhibited increased systemic immune activation and T cell responses after intramuscular and intranasal SARS-CoV-2 immunization, we observed decreased vaccine-induced antibody responses in these animals. These results suggest that early-life viral exposures are sufficient to diminish antibody responses to vaccination in mice, and highlight the potential importance of considering prior microbial exposures when investigating vaccine responses.

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Rotavirus-Induced Expansion of Antigen-Specific CD8 T Cells Does Not Require Signaling via TLR3, MyD88 or the Type I Interferon Receptor

Cited by 4 publications

References 55 publications

Preclinical evaluation of oncolytic potential human rotavirus Wt 1-5 in gastric adenocarcinoma

Preclinical evaluation of oncolytic potential human rotavirus Wt 1-5 in gastric adenocarcinoma

Identification and Characterization of Antigen-Specific T-Cells in Viral Infections

Sequential early-life viral infections modulate the microbiota and adaptive immune responses to systemic and mucosal vaccination

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